Yuzo Ohba

Hemoglobin Mizuho or Beta 68 (E 12) Leucine → Proline, a new Ufistarle Variaiit Associated with Severe Hemolytic Anemia

A hitherto undescribed, unstable hemoglobin was discovered in a four-year-old Japanese girl with relatively severe hemolytic anemia requiring monthly blood transfusion Although no abnormal hemoglobin was detectable by electrophoresis at pll 8.6 and 7.0, heat denaturation and isopropanol tests gave positive results.Chemical analyses of the heat labile henioglohin have demonstrated an amino acid substitution of a prolyl for the leucyl residue at the 68th (E 12) position.Remarkable clinical improvement was observed after splenectomy.

A single nucleotide deletion in codon 123 of the β-globin gene causes an inclusion body β-thalassaemia trait : a novel elongated globin chain βMakabe

Summary. The β‐globin gene from a Japanese individual with an inclusion body β‐thalassaemia trait has been characterized by gene cloning and DNA sequencing. An adenine deletion was detected at the first position of codon 123 (ACC‐CC) of one allele whereas the other allele had a normal sequence. Heterozygosity for this mutation in the patient was confirmed by Southern blots of the genomic DNA digested with HphI, the recognition site of which is eliminated by this deletion. This one base deletion results in the shift of a reading frame in such a manner that the normal termination codon is out of phase. This frameshift mutation results in the synthesis of an elongated β‐globin chain with 10 extra amino acid residues and with an altered C‐terminus. Analysis of labelled globin chains using CM‐cellulose column chromatography failed to demonstrate any abnormal protein, thereby suggesting that the β‐globin chain variant is highly unstable and probably degrades rapidly after synthesis. This event will lead to an accumulation of free α‐chains precipitating in the red blood cells and an inclusion body β‐thalassaemia phenotype would ensue.

Hemoglobin Hirosaki (α 43 [CE 1] Phe→Leu), a new unstable variant

Abstract An electrophoretically silent unstable hemoglobin was discovered in a family with congenital nonspherocytic hemolytic disease. Chemical identification proved it a new variant in which the “invariant” CE 1 phenylalanine is substituted by a leucine in the α chain.

β-Thalassemia in the Korean population

β-Thalassemia is uncommon in the Korean population, however, it must be considered in the differential diagnosis of hypochromic anemia. The molecular characterization of β-thalassemia is absolutely necessary for molecular diagnosis as well as any genetic epidemiological study in this region. We analyzed the molecular basis of β-thalassemia in 38 Korean families. Using direct sequencing of genomic DNA amplified through polymerase chain reaction and haplotype analysis, 35 β-thalassemic genes were characterized, all of which were heterozygous. Twelve different mutations were identified. The most common mutations noted included the initiation codon ATG→AGG (β0) (28.9%), codon 17 (β0) (A→T) (18.4%), and IVS-II-1 (β0) (G→A) (10.5%). Interestingly, mutations causing dominantly inherited β-thalassemia were also common (15.7%). All four cases with the IVS-II-1 (G→A) mutation were linked to the silent mutation of codon 91 (C→T) of the β-globin gene. The initiation codon ATG→AGG and IVS-II-1 (G→A) with codon 91 (C→T) mutations were found in the Far East only, and may be inherited from a common origin for each mutation, at least in Koreans. The codon 17 (A→T) and codons 41/42 (β0) (−TTCT) were suggested to be introduced by gene-flow from southern China. Otherwise, only Hb Korea [codons 33/34 (β0) (−GTG)] and a novel β-thalassemic mutation, codons 89/90 (β0) (−GT), were identified in Koreans. This mutation spectrum is characteristic of the low prevalence area of β-thalassemia in Korea, it is, however, quite different from the adjacent countries, Japan and China.

Source of elevated serum mitochondrial creatine kinase activity in patients with malignancy

Mitochondrial creatine kinase (CK-mit) is increased in cancer tissues of the digestive tract. There is no difference in molecular weight, electrophoretic and kinetic properties between the isoenzymes extracted from the tumor and those from the adjacent normal tissues. High non-CK-M/total CK activity ratios in some sera from cancer patients probably reflect leakage of CK-mit from the tumor tissues.

Hemoglobin Pyrgos (β83 GLY → ASP) in a Japanese Family

A screening survey for abnormal hemoglobins at a hospital in Mizunami city, Gifu prefecture, Japan detected a fast-moving variant of hemoglobin in a family of Japanese origin. The abnormal hemoglobin constitutes about 45 percent of the total hemoglobin from the propositus and another carrier in the family, but neither of these persons had anemia, jaundice, cyanosis or splenomegaly. Structural analysis of this hemoglobin revealed that the amino acid substitution vas at residue 83 in the β chain, where a glycine was replaced by an aspartic acid. Thin hemoglobin variant has been previously reported in a Greek child (hemoglobin Pyrgos) (1). Oxygen affinity of hemoglobin Pyrgos was found to be normal.

Occurrence of Hemoglobin G Cousha in Japan

An abnormal hemoglobin with a substitution of Ala for Glu at the 22nd residue of the β chain has been found in North American Indians (Hbs G Coushatta and G Saskatoon) (1-3), Koreans (Hb G Taegu) (4-6) and Chinese (Hb G Hsin-Chu) (5,6). Blackwell et al (6) assumed that the Chinese and Korean subjects have the same hemoglobin variant because of gene flow. Surveys in the southwestern parts of Japan have uncovered two apparently unrelated families with this variant. This paper deals with the chemical and functional characterization of the Hb G Coushatta found in Japan.The first family was discovered by agar gel electrophoresis at pH 8.6 (7) in 1971 during a survey of patients in Yamaguchi University Hospital. The patient, a 36-year-old female, had been admitted because of ruptured ectopic pregnancy. She had been healthy with no history of either anemia or jaundice. Routine hematology and blood chemistry twenty months later were normal. Her late father, who was assumed to have transmitted the gene for the var...

A Case of Juvenile Erythroleukemia with Uncoordinated Expression of Fetal Red Cell Markers

A 7-year-old boy with juvenile erythroleukemia is described, whose red cells demonstrated a high content of Hb F with fetal structure and yet contained carbonic anhydrase at adult red cell level. The findings seem to exemplify the occurrence of uncoordinated expression of fetal markers and consequently the incomplete reversion to fetal-type erythropoiesis in a hematologic malignancy.

Sporadic case of hemoglobin Bushwick detected by chance in aplastic crisis.

causes of congenital non-spherocytic hemolytic anemia, with over 90 molecular variants of it having been reported so far in the world.1 The US-Hb precipitates within red blood cells (RBC) as insoluble inclusions or Heinz bodies, because of an important abnormality in the primary structure of the globin chain. However, the clinical manifestations of US-Hb are variable and range from chronic hemolytic anemia, which is nearly asymptomatic, to life-threatening severe hemolysis. Human parvovirus (HPV) B19 is known to cause erythema infectiosum and has also been well known to trigger aplastic crisis in patients with chronic hemolytic anemia.2 Sometimes it may cause the first episode of anemia in patients with previously undetected US-Hb and has led to their diagnosis. We experienced a sporadic case of hemoglobin (Hb) Bushwick, a case that resulted from sporadic mutation and presented clinically with aplastic crisis due to HPV B19 infection.

Unstable Hemoglobinemia, Hb Buenos Aires, Bryn Mawr, Followed Up for Eighteen Years

A 20-year-old man has been under observation for 18 years because of unstable hemoglobinemia, Hb Buenos Aires, Bryn Mawr (beta-globin, Phe85Ser). At the age of 19 years, he was hospitalized because of fever and hemolytic crisis, and the symptoms resolved after infusion of antibiotics. Nucleotide sequencing of the beta-globin gene confirmed that the patient was heterozygous for the mutation. The patients erythrocytes showed an increased affinity for oxygen and a prolonged glycerol lysis time. We review a previously reported single family and 5 other cases, and discuss the clinical significance of splenectomy and plasma-derived haptoglobin.